title: CD8+ Treg cells suppress CD8+ T cell-responses by IL-10-dependent mechanism during H5N1 influenza virus infection.
abstract: Although Treg-cell-mediated suppression during infection or autoimmunity has been described, functions of Treg cells during highly pathogenic avian influenza virus infection remain poorly characterized. Here we found that in Foxp3-GFP transgenic mice, CD8(+) Foxp3(+) Treg cells, but not CD4(+) Foxp3(+) Treg cells, were remarkably induced during H5N1 infection. In addition to expressing CD25, the CD8(+) Foxp3(+) Treg cells showed a high level of GITR and produced IL-10. In an adoptive transfer model, CD8(+) Treg cells suppressed CD8(+) T-cell responses and promoted H5N1 virus infection, resulting in enhanced mortality and increased virus load in the lung. Furthermore, in vitro neutralization of IL-10 and studies with IL-10R-deficient mice in vitro and in vivo demonstrated an important role for IL-10 production in the capacity of CD8(+) Treg cells to inhibit CD8(+) T-cell responses. Our findings identify a previously unrecognized role of CD8(+) Treg cells in the negative regulation of CD8(+) T-cell responses and suggest that modulation of CD8(+) Treg cells may be a therapeutic strategy to control H5N1 viral infection.
authors.affiliation: Key laboratory of Medical Molecular Virology of MOH and MOE, Fudan University Shanghai Medical College, Shanghai, China; State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zou
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.forename: Jia
authors.initials: J
authors.lastname: Xue
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Fan
authors.forename: Congcong
authors.initials: C
authors.lastname: Feng
authors.forename: Shuang
authors.initials: S
authors.lastname: Geng
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000378:metabolism; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D053701:Receptors, Interleukin-10 / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019076:Transgenes / Q000235:genetics; D019562:Viral Load
chemical_list: D019138:Antibodies, Blocking; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053450:Glucocorticoid-Induced TNFR-Related Protein; D053701:Receptors, Interleukin-10; C491405:TNFRSF18 protein, human; D016753:Interleukin-10
keywords: CD8+ Treg cells; H5N1 influenza virus; IL-10